This proposal is designed to provide a diverse and extensive research experience in molecular biology that will allow the applicant to develop into a mature scientist-clinician with an outstanding potential to contribute to both academic ophthalmology and basic science research. The research training has two main components: I) advanced basic science training and 2) thesis research leading to the Ph.D. in Biological Chemistry. All components of training are incorporated in the curriculum of the EyeSTAR program based at UCLA. The advanced basic science component includes course work, seminars and undergraduate teaching. The course work will cover a variety of topics including macromolecular structure and metabolism, subcellular organization and computer statistics. Research experience consists of two quarterly laboratory rotations and a thesis research project. The thesis project will focus on the investigation of regulatory mechanisms controlling expression of the gene encoding the beta-subunit of human rod-specific phosphodiesterase (beta-PDE). It has been previously documented that defective levels of PDE activity due to genetic defects in the beta-PDE gene are directly responsible for the development of the specific phenotype in the retinal degeneration (rd) mouse. Genetic mutations have been reported in the beta-PDE gene in human in association with certain forms of autosomal recessive retinitis pigmentosa, the leading cause of blindness worldwide. It is our hypothesis that with current advances in gene-specific therapy, identification, characterization and experimental testing of the transcription factors controlling the expression of this gene in human would set the stage for new therapeutic modalities in the future. Dr. Debora Farber is nationally recognized for her biochemical and molecular biological studies of retinal degenerations, in particular retinitis pigmentosa. Dr. Farber will serve as mentor for the PI's thesis research. In addition, UCLA has an outstanding panel of faculty members many of whom have professional relationships with Dr. Farber and can serve as scientific consultants to the PI. The pivotal role played by transcription factors in the regulation of gene expression ensured that this project will be at the cutting edge of current research and is an ideal area with which to begin a scientific career. The EyeSTAR program also incorporates three years of clinical training in ophthalmology leading to certification and specialty board eligibility. This intense three-year residency program provides a vast clinical experience in diagnosis and treatment of the complete scope of ophthalmologic problems as well as a number of didactic activities including lectures, special seminars, and attendance at clinical research meetings.